This project's aim is to identify key intracellular mechanisms underlying neuroendocrine regulation of gonadotropin secretion by the gonadal steroids. Radioimmunoassay and neurochemical techniques will measure a). patterns of gonadal steroid nuclear uptake and pituitary luteinizing hormone (LH) release, and b). concurrent changes in pituitary responsiveness to gonadotropin releasing hormone (GnRH) associated withl steroid treatments which suppress tonic, or basal LH release or stimulate cyclic, or preovulatory, LH release in the rat. Timed studies with the antiestrogen CI-628 and 3H-estradiol will be conducted to determine whether estrogen receptor translocation to the cell nucleus in brain and/or pituitary cells in obligatory for the rapid (within 1 hour) feedback actions of estradiol on LH release. Estradiol uptake patterns necessary for inducing cyclic LH release will also be determined with an "exchange assay" that measures estradiol-receptor complexes in purified nuclear pellets of brain and pituitary tissues. This assay will also be used to determine if androgen conversion to estrogen is obligatory for androgen suppression of tonic LH release. Finally, genetically, psuedohermaphrodite rats will be used to localize sites of androgen feedback to the brain or pituitary gland.